The Johns Hopkins Lupus Cohort is a longitudinal study, begun by Dr. Petri in 1987, of the incidence and pathogenesis of thrombotic events (TE) and coronary artery disease (CAD) in 225 patients with systemic lupus erythematosus (SLE) (60.2% black, 90.5% female, mean age 36.5 years). In SLE, both TE and CAD are a major cause of morbidity. The usual natural history of TE and CAD is telescoped, so that patients can present with these outcomes in their third and fourth decades. In our cohort study to date, 44 patients, have had past and 10 patients have had prospectively-followed thrombotic events. Thirteen patients (6.6%) have had coronary artery disease. We have prospectively followed our lupus cohort routinely every three months and have amassed a four-year database specifically designed to identify and to follow over time the most important risk factors for TE and CAD. Risk factors to be addressed in the study include: 1) the hypercoagulable state secondary to antiphospholipid antibodies (the lupus anticoagulant and anticardiolipin antibody); 2) premature atherosclerosis, accelerated by prednisone and hypertension; 3) underlying vascular damage from lupus vasculopathy and vasculitis; 4) co-morbid factors, including obesity, smoking, hyperlipidemia, hypertension, sedentary life style, and family history of CAD, and 5) other factors, including sex, age, race, immunogenetics, compliance with medication, and socioeconomic status. The Hopkins Cohort Study is uniquely able to focus on these issues, both because of its population, which reflects a broad racial, educational, and socioeconomic background, and because the four years of data accumulated to date show promising preliminary results. The five years of the proposed study will allow us to address further the incidence of TE and CAD, the importance of identified risk factors both singly and in combination, and to begin to address the issue of intervention to modify and reduce risk factors.